plinabulin (BPI 2358) / BeyondSpring, Jiangsu Hengrui Pharma - LARVOL DELTA

Plinabulin to shorten neutropenia and improve quality of life peri-autologous hematopoietic cell transplant. (ASCO 2023) - P2 | "To decrease the period of myelosuppression and obligate neutropenia after high dose melphalan with autologous hematopoietic stem cell transplantation (AHCT) for patients with multiple myeloma, we studied the addition of plinabulin to standard growth factors. To achieve the primary objective of reducing the duration of absolute neutropenia post AHCT, 40mg of intravenous plinabulin was given 1-3 hours after stem cell infusion (Day 0) with pegfilgrastim on Day +1 in this pilot trial (NCT05130827)... Plinabulin appears well tolerated without additional major toxicities post AHCT and provided a high WBC on Day +2 and decreased rate of neutropenic fever. Plinabulin PK, quality of life data, and PROs will be presented. Adjusting the schedule of plinabulin to later post AHCT pre engraftment may further shorten the duration of neutropenia using this novel mechanism of action."

HEOR • Bone Marrow Transplantation • Cardiovascular • Chemotherapy-Induced Neutropenia • Febrile Neutropenia • Hematological Disorders • Hematological Malignancies • Hypertension • Immune Modulation • Multiple Myeloma • Neutropenia • Oncology • Solid Tumor • Transplantation • CD34

Plinabulin/Docetaxel vs. Docetaxel in 2L/3L NSCLC after Platinum Regimens (DUBLIN-3): A Phase 3 Randomized Controlled Trial (IASLC-WCLC 2024) - P3 | "Conclusions : In patients with advance EGFR wild-type platinum refractory NSCLC, plinabulin combined with docetaxel was well-tolerated and statistically significantly improved OS/PFS/ORR with reduced severe neutropenia. A durable anti-cancer benefit was observed suggesting that plinabulin/docetaxel as a potential practice-changing treatment for advanced/metastatic NSCLC without driver mutations."

Clinical • P3 data • Cardiovascular • Gastroenterology • Gastrointestinal Disorder • Hematological Disorders • Hypertension • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Neutropenia • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR

BeyondSpring Reports Second-Quarter 2026 Financial Results and Provides Corporate Update (GlobeNewswire) - "Research and development (R&D) expenses were $1.0 million for the quarter ended June 30, 2026, compared to $1.0 million for the quarter ended June 30, 2025. R&D expenses remained relatively flat, as a $0.3 million increase in drug manufacturing activities to prepare for potential future study initiation was substantially offset by lower patent-related professional services and personnel expenses."

Commercial • Non Small Cell Lung Cancer

Pembrolizumab in Combination With Plinabulin and Docetaxel For Metastatic NSCLC After ICIs (KeyPemls-004) (clinicaltrials.gov) - P2 | N=47 | Active, not recruiting | Sponsor: Peking Union Medical College Hospital | Trial completion date: Dec 2025 ➔ Dec 2026

Trial completion date • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • EGFR • ROS1

Design, Synthesis, and Evaluation of Antitumor Activity of Novel Phenylahistin Derivatives with Double F-Substitution via Dual Inhibition of Microtubule and P53/BCL-2/BAX Signaling Pathways. (PubMed, J Med Chem) - "Plinabulin, a derivative of phenylahistin, is a microtubule-protein inhibitor that is being studied as a potential antitumor agent. This led to mitochondrial dysfunction and a significant increase in reactive oxygen species (ROS) levels in tumor cells, ultimately inducing tumor cell apoptosis. Importantly, compound 45 not only surpassed docetaxel in inhibiting tumor growth in the mouse allograft model using LLC cells but also demonstrated a good safety profile."

IO biomarker • Journal • Lung Cancer • Metabolic Disorders • Oncology • Solid Tumor • BCL2

BeyondSpring Presents the Latest Update of a Phase 2 Study Demonstrating Durable Clinical Benefit of Pembrolizumab Plus Plinabulin/Docetaxel in Metastatic NSCLC After Progression on First-Line Immune Checkpoint Inhibitor Therapy at ASCO 2026 (The Manila Times) - "Meaningful clinical benefit: Median PFS at 7.0 months, median DoR is 9.3 months with DCR of 79.5% in metastatic NSCLC patients with acquired resistance to immune checkpoint inhibitors...Good tolerability and immune activation: Along with increased frequencies of activated CD4+/CD8+ T cells post-treatment, hematology test also showed safety benefit with significantly higher levels of WBCs, neutrophils and platelets...12-Month Overall Survival (OS) Rate: 78.1%; 24-Month OS Rate: 58.0%, with median OS not reached"

P2 data • Non Small Cell Lung Cancer

A phase 2 study of plinabulin (Plin)/docetaxel (Doc) plus pembrolizumab (Pemb) in metastatic NSCLC (mNSCLC) after acquired resistance (AR) to anti–PD-1/L1 alone or in chemotherapy combination: Efficacy and immunophenotyping. (ASCO 2026) - P2 | "Plin/doc plus Pemb shows promising efficacy in mNSCLC with AR to anti-PD-1/L1 confirmed by immune activation post-treatment. TRAEs were manageable. These findings along with DUBLIN-3 support a global confirmatory study in EGFR/ALK wild-type NSQ NSCLC following progression on anti-PD1/L1 based therapy."

Clinical • Metastases • P2 data • Preclinical • Hematological Disorders • Lung Cancer • Neutropenia • Non Small Cell Lung Cancer • Solid Tumor • CD4 • CD8 • EGFR

BeyondSpring Inc…announced an upcoming poster presentation of Study 303, an investigator-initiated study supported by Merck…and BeyondSpring, in patients with 2L/3L NSCLC who progressed on PD-1/PD-L1 inhibitors, at the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting, taking place May 29 through June 2 in Chicago, IL. (The Manila Times)

P2 data • Non Small Cell Lung Cancer

Plinabulin boosts antitumor efficacy of topoisomerase inhibitor-based antibody-drug conjugates without or with immune checkpoint inhibitor (AACR 2026) - "Preclinically, Plin boosts irinotecan activity in human colon cancer models and reduces topotecan-induced neutropenia. Here we investigated Plin synergy with TOP1-ADC in-vitro, and with or without PD-1/L1 inhibitor pembrolizumab (Pembro) or atezolizumab (Atezo) in-vivo. For combinations in-vitro, HER2+ KPL-4 breast cancer cells were treated with Plin (1.46 - 46.8 nM), T-DXd (0.105 - 3.37 μM) or both. For combinations in-vivo, MC38 mouse colon adenocarcinoma cells overexpressing hTROP2 (hTROP2-MC38) or hHER2 (hHER2-MC38), were inoculated in B-hPD-1 or B-hPD-1/hPD-L1/hHER2 mice respectively, and antitumor activities of Plin (7.5 mg/kg) plus Dato-DXd (5 mg/kg) ± Pembro (0.3 mg/kg) or T-DXd (3 mg/kg) ± Atezo (8 mg/kg) were evaluated. On HER2+ KPL-4 cells, Plin showed synergistic activity with T-DXd with median CI <1 at 1:1, 2:1 and 4:1 ratios (T-DXd:Plin)... Plinabulin is a Phase 3 novel agent clinically validated to promote DC maturation and T-cell activation,..."

ADC • Checkpoint inhibition • Clinical • Breast Cancer • Colon Adenocarcinoma • Colon Cancer • Colorectal Adenocarcinoma • Colorectal Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • HER-2 • PD-L1 • TACSTD2 • TOP1

BeyondSpring Reports Compelling New Data: Plinabulin Advances Both the Anticancer Efficacy and Safety of ADC Drugs (GlobeNewswire) - "Stronger anticancer activity: Complete tumor regressions were more frequent and animals survived significantly longer — in both two-drug (ADC+ Plinabulin) and three-drug (ADC+ Plinabulin + PD-1 inhibitor) combinations (PD-1 inhibitors are immunotherapies that activate the body’s own immune system to fight cancer). Better tolerability to potentially keep patients on therapy: Plinabulin reduced animal death in both two-drug and three-drug combinations....Immune system activation: Analysis showed that Plinabulin enhanced the body’s own cancer-fighting T-cells, significantly increasing CD8+ T cell/Treg ratio — providing a biological explanation for why the combination outperforms either drug alone."

Preclinical • Oncology

Mechanism of Gzma-mediated GEF-H1 activation in intestinal epithelial cells leading to intestinal barrier dysfunction in sepsis. (PubMed, Clin Transl Med) - "Gzma induces the dephosphorylation of Ser886 on GEF-H1, activating the RhoA/ROCK pathway and disrupting the intestinal epithelial barrier. Knocking out GEF-H1 can alleviate intestinal damage, protect multiple organs, and increase the survival rate of septic mice. Epothilone A inhibits the activation of GEF-H1, thereby restoring the barrier function and reducing the mortality rate of sepsis."

Journal • Infectious Disease • Septic Shock • CDH1 • CLDN1 • GZMA • OCLN • RHOA • TJP1

The novel microtubule-destabilizing compound AUS_001 maintains unique binding to the colchicine site of tubulin and elicits reversible cellular effects relative to other anti-tubulin agents (AACR 2024) - "Comparison of the tubulin-AUS_001 complex structure with the ones of tubulin-colchicine and tubulin-plinabulin revealed that AUS_001 elicits different rearrangements in the T7 loop of β-tubulin versus colchicine and occupies a different zone of the pocket relative to plinabulin, further elaborating its unique binding properties...Conversely, colchicine, CA-4 or paclitaxel administered at the same doses as those applied for AUS_001 failed to reverse the drug-induced phenotypes upon removal resulting in sustained cytotoxicity. In conclusion, we fully characterized the unique binding mode of AUS_001 to the colchicine site of tubulin and elucidated the reversible nature of the target engagement. AUS_001 features a distinctive and reversible molecular interaction with tubulin which provides a plausible explanation for its favorable safety profile compared to other microtubule targeting agents."

Brain Cancer • CNS Tumor • Gastrointestinal Cancer • Glioma • Oncology • Pancreatic Cancer • Solid Tumor

BeyondSpring Announces Plinabulin and ADC Combination Poster Presentation at AACR Annual Meeting 2026 (GlobeNewswire)

Preclinical • Solid Tumor

…BeyondSpring plans to initiate the global Phase 3 DUBLIN-4 confirmatory study, focusing on a mechanism-enriched patient population of EGFR wild-type non-squamous NSCLC progressed on prior PD-1/L1 inhibitors with overall survival as the primary endpoint (NCT07361484) (GlobeNewswire)

Trial status • Lung Non-Squamous Non-Small Cell Cancer

BeyondSpring to Participate at the 12th Annual Immuno-Oncology 360° Conference (GlobeNewswire) - "Dr. Lan Huang, Co-Founder, Chairman, and CEO of BeyondSpring, will present on Plinabulin as a differentiated immuno-oncology asset designed to enhance PD-1/PD-LD blockade and highlight Plinabulin’s unique mechanism of action and clinical development strategy."

Clinical • Non Small Cell Lung Cancer • Small Cell Lung Cancer

Docetaxel Plus Plinabulin vs Docetaxel Plus Placebo in Advanced/Metastatic Non-Squamous NSCLC After PD-1/PD-L1 Therapy and Platinum Chemotherapy (DUBLIN-4) (clinicaltrials.gov) - P3 | N=442 | Not yet recruiting | Sponsor: BeyondSpring Pharmaceuticals Inc.

New P3 trial • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Neutropenia • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • EGFR

Study of Plinabulin and Pegfilgrastim in People With Multiple Myeloma Undergoing an Autologous Hematopoietic Stem Cell Transplant (AHCT) (clinicaltrials.gov) - P2 | N=17 | Active, not recruiting | Sponsor: Memorial Sloan Kettering Cancer Center | Trial primary completion date: Nov 2025 ➔ Nov 2026 | Trial completion date: Nov 2025 ➔ Nov 2026

Trial completion date • Trial primary completion date • Bone Marrow Transplantation • Hematological Disorders • Hematological Malignancies • Multiple Myeloma • Neutropenia • Oncology • Transplantation • CD34

Plinabulin/docetaxel vs. docetaxel in 2L/3L EGFRwt NSCLC after platinum regimens (DUBLIN-3): Asian subgroup analysis (ESMO Asia 2025) - "In the Asian subgroup analysis, plinabulin/docetaxel significantly improved OS/PFS/ORR with reduced severe neutropenia, especially in NSQ pts. The durable survival benefit is supported by plinabulin's mechanism ofDC maturation and T cell activation. The positive benefit/risk ratio over docetaxel suggests a potential practice-changing treatment."

IO biomarker • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

BPI-2358 reprograms immunosuppressive macrophages and impairs leukemic progression in MN1-overexpressing AML In Vivo (ASH 2025) - "This was further supported by asignificant decrease in spleen weight in the BPI-2358-treated group. These findings reinforce thepotential of macrophage reprogramming as a complementary strategy in AML treatment, especially inmolecularly high-risk subtypes such as those associated with MN1 overexpression."

Preclinical • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • ANXA5 • CD14 • CD163 • CD34 • CD80 • CD86 • IL1B • IL6 • KIT • MN1 • MRC1 • NOS2 • TGFB1 • TNFA

BeyondSpring Announces New Analyses of DUBLIN-3 Phase 3 Study Showing Survival Benefit of Plinabulin + Docetaxel in Post Anti-PD-(L)1 for Non-squamous EGFR WT NSCLC and a Reduction in Brain Metastasis Compared to Docetaxel at NACLC 2025 (GlobeNewswire) - "Median overall survival (OS): DP 15.8 months vs. D 11.7 months (HR=0.55); Median progression-free survival (PFS): DP 5.6 vs. D 3.8 months (HR=0.67); Objective response rate (ORR): 18.2% vs. 8.0%...Post-hoc analysis of DUBLIN-3 intent-to-treat (ITT, N=559) EGFR WT NSCLC population showed additional clinically meaningful benefits for the Plinabulin + docetaxel combination compared to docetaxel: Meaningful improvement in metastasis-free survival: Metastasis-free survival improved to 15.34 months (DP) versus 7.7 months (D, HR=0.52, p=0.0012), consistent with Plinabulin’s DC maturation and durable anti-cancer benefit...The incidence of new brain metastasis was reduced to 4.32% (DP) vs. 7.83% (D), consistent with Plinabulin’s brain-penetrant properties which demonstrated survival benefit in glioblastoma anal model as a monotherapy."

P3 data • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer

BeyondSpring plans to initiate a global Phase 3 DUBLIN-4 trial following its End-of-Phase 2 meeting with the U.S. FDA. (GlobeNewswire) - "This study will evaluate Plinabulin + docetaxel vs. docetaxel in non-squamous EGFR wild-type NSCLC after progression on anti-PD-(L)1 and chemotherapy, and is intended to serve as the global confirmatory study."

New P3 trial • Lung Non-Squamous Non-Small Cell Cancer

Plinabulin and Selumetinib Enhance M1 Macrophage Traits and Trigger Cell Death in AML (ASH 2024) - "Additionally, both drugs were associated with reduced mitochondrial membrane potential in leukemic blasts and AAMs, suggesting an impact on mitochondrial metabolism. In conclusion, we found that both BPI-2358 and AZD6244 exhibit potential in repolarizing M2-like TAMs towards an M1-like phenotype, and have cytotoxic activity in AAM and leukemic blasts thus representing a promising avenue for enhancing AML treatment strategies."

Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • CD14 • CD163 • CD34 • CD80 • CD86 • HOXA9 • KIT • MN1 • MRC1 • TNFA

Nivolumab in Combination With Plinabulin in Patients With Metastatic Non-Small Cell Lung Cancer (NSCLC) (clinicaltrials.gov) - P1 | N=18 | Completed | Sponsor: Lyudmila Bazhenova, M.D. | Active, not recruiting ➔ Completed

Trial completion • Lung Cancer • Lung Non-Small Cell Squamous Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Resensitize Patients with Eight Cancer Types Who Failed Prior PD-1/L1 Inhibitors with Disease Control Rate of 54% through DC Maturation and M1 Macrophage Polarization via GEF-H1-dependent Mechanism in Phase 1 Clinical Study (GlobeNewswire) - "This phase 1 investigator-initiated study (NCT04902040, MD Anderdon Cancer Center) shows that in addition to potent DC maturation for a systemic immune response, plinabulin combined with radiation and PD-1 inhibitor promotes proinflammatory monocytes and M1 macrophage polarization via a Plinabulin specific GEF-H1-dependent mechanism with the potential of overcoming acquired resistance to immune checkpoint inhibitors from pro-tumor macrophages."

P1 data • Hepatocellular Cancer • Non Small Cell Lung Cancer • Renal Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

Resensitize NSCLC Patients Who Progressed on Prior PD-1/L1 Inhibitors with Disease Control Rate of 85% in Phase 2 Clinical Study (GlobeNewswire) - "New data from a phase 2 investigator-initiated study (NCT05599789, Peking Union Hospital China) evaluating Plinabulin, docetaxel, and pembrolizumab in metastatic NSCLC patients who progressed on prior PD-1/L1 inhibitors (n=47), showed encouraging efficacy and safety data. The combination demonstrated median progression-free survival (PFS) of 7.0 months, confirmed objective response rate (ORR) of 18.2%, duration of response (DOR) of 7.2 months, disease control rate (DCR) of 85%, and 12-month overall survival (OS) rate at 79%, and 24-month OS rate at 66% (median OS not reached)."

P2 data • Non Small Cell Lung Cancer